<icnmgrjill> GREETINGS EVERYONE AND WELCOME TO THE ICN CHAT FOR MAY 18, 1999 OUR SPEAKER TONIGHT IS DR. KEN PETERS OF BEAUMONT HOSPITAL IN ROYAL OAK MICHIGAN. DR. PETERS IS THE LEADING RESEARCHER OF BCG IN THE UNITED STATES AND HAS PUBLISHED REGULARLY IN THE UROLOGY JOURNALS.

<icnmgrjill> BEFORE WE GET STARTED, I'D LIKE TO REMIND YOU ALL OF OUR DISCLAIMER: Active, informed IC patients understand implicitly that no patient, no web site, online meeting or e-mail is medical advice. Under no circumstance should you consider this information a substitute for face to face medical care with a trusted personal physician. They, and only they, should make medical recommendations to you.

<icnmgrjill> WELCOME DR. PETERS! THANK YOU FOR SPEAKING WITH US TONIGHT

<drpeters> thank you for inviting me here tonight

<icnmgrjill> WE HAVE A PREPARED PRESENTATION ON BCG FIRST AND THEN WE'LL TAKE Q&A. IF YOU HAVE A QUESTION FOR DR. PETERS, PLEASE WHISPER IT TO ME, DIANE OR JULIE AND WE'LL PUT YOU IN THE QUEUE

--------------- PRESENTATION BEGINS ----------------

The History of BCG:

<presentation> Bacillus Calmette Guerin (BCG) is a vaccine comprised of a live, weakened strain of the tuberculosis bacteria.

<presentation> In 1929, BCG was shown to be protective against cancer

<presentation> BCG is instilled in the bladder and is the most effective treatment for superficial bladder cancer

<presentation> BCG is thought to treat cancer by stimulating the immune system

<presentation> * 5 reported deaths from BCG in past 12 years during its use in bladder cancer (most were prior to gaining experience in using intravesical BCG)

The First reported use in IC:

<presentation> In 1993, Dr. Zeidman presented the use of BCG for the treatment of IC at our national meeting

<presentation> He reported that 4 of 5 IC patients treated with BCG had improvement in their symptoms

<presentation> When asked why he treated IC with BCG, he related a story of a patient who he thought had IC, but he performed cystoscopy with bladder biopsy and her biopsy demonstrated cancer, rather than IC

<presentation> Thus, he treated the patient with BCG and all of her "IC symptoms" resolved.

<presentation> The pathologist informed Dr. Zeidman that he had made a mistake and there was no cancer in the specimen

<presentation> The patient truly had IC and she appeared to improve with BCG. This prompted him to treat 4 other IC patients

<presentation> I was present at Dr. Zeidman's talk and felt that BCG was worthy of further investigation for the treatment of IC

Placebo Controlled Trials:

<presentation> In 1994, I began a prospective, double-blind placebo-controlled trial to study the effect of BCG on IC symptoms

<presentation> Thirty patients were enrolled in the trial and received either 6 weekly bladder instillations of BCG or placebo (water)

<presentation> Patients were followed for six months and at the end of the trial, 60% of the BCG patients had marked improvement in symptoms compared to 27% of placebo patients (Journal of Urology, vol. 157, 2090-2094, 1997)

<presentation> The placebo patients were then treated with BCG and 67% had clinical improvement

<presentation> Patients who received BCG and improved were followed at 6 month intervals and with a minimum of 2 years follow-up, 90% of patients who responded to BCG remained improved without any further treatment of their IC. In addition, these patients were off all of their IC medications and pain meds. (Journal of Urology, Vol. 159, 1483-1487, 1998)

<presentation> The number of reported side-effects were identical between patients who received BCG compared to placebo

<presentation> Most reported side effects were irritative voiding symptoms with the instillations (increase frequency, burning, and urgency)

<presentation> Most serious side effect was joint pain in 3 patients. The pain was significant and lasted approximately 3 months. The pain always resolved and each of these patients had improvement in their bladder symptoms

Why might BCG treat Interstitial Cystitis?

<presentation> There is evidence in the literature that IC may be secondary to an imbalance in the immune system leading to chronic inflammation of the bladder

<presentation> BCG stimulates the opposite end of the immune system which may correct this imbalance, leading to a long-term improvement

<presentation> We recently demonstrated that immune markers are elevated in the urine of IC patients and are normal in IC patients who responded to BCG

<presentation> We are currently investigating the relationship of the immune system in IC, and hope to find a specific change that needs to occur which will lead to clinical improvement

Current status of BCG for the treatment of IC:

<presentation> An international phase III trial is underway at multiple sights in the United States and Europe

<presentation> We will await the results of this trial to confirm what was found in the phase II trial

<presentation> If BCG is an effective treatment for IC, we will pursue approval of this drug through the FDA.

Two last points: BCG should not be used with Elmiron because Elmiron inhibits the effectiveness of BCG and its important for everyone to understand that it will take about 3 months to know if it works. Patients do not feel better right away.

--------------- PRESENTATION ENDS ----------------

--------------- QUESTIONS & ANSWERS BEGINS ----------------

<icnmgrjill> THANK YOU DR. PETERS! WE APPRECIATE THAT VERY QUICK LOOK AT BCG. NOW... WE'VE GOT SOME EXCELLENT QUESTIONS FOR YOU FROM THIS VERY EDUCATED GROUP OF IC PATIENTS. SO LETS GO AHEAD AND TAKE THEM... ONE AT A TIME...

<icnmgrjill> QUESTION #1 IS FROM JULIE S. SHE WANTS TO KNOW WHAT THE CORRECT DOSAGE FOR BCG IS.. HER DOCTOR ONLY KNOWS THE CANCER DOSAGES... IS IT THE SAME OR DIFFERENT??

<drpeters> The dosage for we've used for IC patients is the same that we use for bladder cancer.

<icnmgrjill> QUESTION #2 IS FROM MARY. SHE WANTS TO KNOW HOW LONG PATIENTS NEED TO RETAIN THE BCG??

<drpeters> the ideal time is two hours However, clearly not every IC patient can hold it for this long. We ask them to hold it as long as possible for a minimum of 30 minutes.

<icnmgrjill> QUESTION #3 IS FROM MINDY. SHE WANTS TO KNOW IF YOU ONLY YOU BCG ON YOUR SEVERE PATIENTS?? WHAT ABOUT THE ONES WITH LESSER CASES OF IC?

<drpeters> I believe BCG is better for the mild to moderate symptoms. We use it on all IC patients and we are trying to see if we can determine the ideal patient population.

<icnmgrjill> QUESTION #4.. COMES FROM MATTS MOM. SHE WANTS TO KNOW WHAT HAPPENED TO THE FIFTH PATIENT IN THAT STUDY.

<drpeters> The fifth patient in Dr. Zeidman's study did not improve. I do not know how she did. However, in our study, the patients who did not improve were no worse at the end of the study

<icnmgrjill> QUESTION #5.. IS FROM HOPE. RIGHT NOW ELMIRON APPEARS TO BE THE FIRST CHOICE FOR IC TREATMENTS. DO YOU SEE BCG BECOMING THAT FIRST CHOICE IN PLACE OF ELMIRON IN THE FUTURE?

<drpeters> We will have to await the results of the current study to answer that question.

<icnmgrjill> QUESTION #6 COMES FROM MARE. SHE WANTS TO KNOW IF PATIENTS WHO HAVE TESTED POSITIVE FOR TB VIA A SKIN TEST WOULD BE EXCLUDED FROM THE TREATMENT?

<drpeters> In the current study they are excluded so that we have a "like" patient population. However this is not definitely a contraindication. In addition, you can convert to PPD positive after intravesical BCG treatments.

<icnmgrjill> QUESTION #7 CONTINUES THIS LINE OF THOUGHT FROM DIANE.SHE WANTS TO KNOW IF PATIENTS CAN BECOME INFECTED WITH THE TB VIRUS AFTER TREATMENT??

<drpeters> One of the risks of BCG is becoming ill from the treatment with high fever, chills or sepsis. It is unlikely to actually contract TB. The risk of a serious side effect is low based on our experience in bladder cancer and would occur more likely in men due to catheterization of the prostate and potential bleeding associated with this.

<icnmgrjill> QUESTION #8 COMES FROM HROY. SHE WANTS TO KNOW IF BCG WILL HELP WITH LEAKAGE AND INCONTINENCE

<drpeters> No

<icnmgrjill> QUESTION #9.. IS FROM BILL. HE WANTS TO KNOW IF THERE IS A DIFFERENCE BETWEEN MALE AND FEMALE RESPONSE TO TREATMENT??

<drpeters> In the initial studies, BCG was only used in females, however, the current study is enrolling male IC patients

<icnmgrjill> HE ALSO HAS THE NEXT QUESTION.. ND WANTS TO KNOW WHAT PERCENTAGE OF POSITIVE RESPONDERS COULD BE CLASSIFIED AS IN REMISSION?

<drpeters> The majority of responders (90%) maintained a marked improvement in symptoms or over two years. Those who respond seem to get better over time

<icnmgrjill> QUESTION #10.. IS FROM CLAIRE. HE WANTS TO KNOW IF BCG EVER MAKES ANYONE WORSE OFF AFTERWARDS?

<drpeters> BCG can make symptoms somewhat worse during the treatment phase of the study. However, no patient has been worse off in the long run. Further studies need to confirm this observation.

<icnmgrjill> SHE ALSO WANTS TO KNOW IF IT CAN HELP PATIENTS WHO HAVE URGENCY?

<drpeters> In our initial studies the urgency was improved in those who responded

<icnmgrjill> THE NEXT QUESTION IS FROM JULIE. SHE SAYS..."WE KNOW THAT BCG STIMULATES THE IMMUNE SYSTEM, BUT DOES IT DO ANYTHING ELSE IN THE BLADDER (I.E. LIKE REPAIR THE BLADDER MUCOSA)?"

<drpeters> I believe that BCG may treat the underlying cause of IC, which results in a leaky mucosa, thus improving symptoms long-term.

<icnmgrjill> AND... THE NEXT LOGICAL QUESTION...WHAT DO YOU THINK THE CAUSE OF IC IS??

<drpeters> This is under intense study. Recently there is evidence that IC may be caused by over stimulation of one arm of "t: immune system and this overstimulation can be measured in the urine based on preliminary studies. BCG is known to stimulate the opposite end of the immune system. This is only a theory based on preliminary data and a large study is underway to sort this out.

<icnmgrjill> QUESTION #11 IS ABOUT SMOKING, BCG AND IC. CAN SMOKING MAKE IC WORSE??

<drpeters> I believe smoking does make IC worse

<icnmgrjill> CAN SMOKING DECREASE OR HAVE AN ADVERSE EFFECT ON BCG??

<drpeters> There is no evidence of this

<icnmgrjill> QUESTION #12: THIS IS FROM CHRIS... HE MENTIONS THAT HE'S BEEN ON ELMIRON AND HAS HAD BCG TREATMENTS. ANY COMMENTS ON AN ORDER OF TREATMENT?? OR HOW LONG SOMEONE SHOULD WAIT FROM STOPPING ELMIRON... BEFORE STARTING BCG.. OR VICE VERSA

<drpeters> In the test tube, Elmiron is known to bind BCG which, in theory, can inhibit its effect. I recommend stopping Elmiron for at least 6 weeks

<icnmgrjill> QUESTION #13: MINDY WANTS TO KNOW IF PATIENTS WHO BEGIN BCG.. SHOULD STOP SOME OF THE TREATMENTS THAT THEY ARE ALSO TAKING... SUCH AS DITROPAN? OR VISTARIL?

<drpeters> BCG can be used with Ditropan or Vistaril. You should not be on steroids or immunosuppressed.

<icnmgrjill> SEVERAL PEOPLE HAVE ASKED FOR THE DOSAGE INFO...

<drpeters> The dose is the standard bladder cancer dose. It is one vial (50 mg) of BCG in 50 cc of saline, instilled once a week for 6 weeks

<icnmgrjill> QUESTION #14: MARY ASKS.. SOME IC PATIENTS HAVE TROUBLE TOLERATING CATHETERIZATION. WHEN YOU INSTILL BCG...CAN THE CATHETER BE REMOVED WHILE THE PATIENT IS HOLDING IT?? TO REDUCE DISCOMFORT, ETC.

<drpeters> yes

<icnmgrjill> SHE ALSO WANTS TO KNOW IF YOU RECOMMEND THE USE OF LIDOCAINE BEFORE THE TREATMENT?

<drpeters> lidocaine can kill bcg, thus I recommend not using lidocaine jelly

<icnmgrjill> SUSAN WANTS TO KNOW IF THERE IS A SIMILAR COMPLICATION BETWEEN BCG & DMSO???

<drpeters> I know of no data on the compatibility of DMSO and BCG

<icnmgrjill> QUESTION #15: MINDY WANTS TO KNOW ABOUT PATIENTS WHO JUST CAN'T TOLERATE CATHETERIZATIONS. WHAT CAN BE DONE FOR THEM TO MAKE THE TREATMENT PROCESS EASIER??

<drpeters> This is a difficult problem, however, the catheterization needs only to be performed six times and I don't know of a way to make this easier other using a small pediatric catheter

<icnmgrjill> FOLKS.. WE'RE JUST GOING TO TAKE A FEW MORE QUESTIONS! DR. PETERS HAS BEEN VERY GENEROUS WITH HIS TIME. THE NEXT QUESTION IS FROM DIANE. SHE HAS HAD SEVERAL BCG TREATMENTS BUT HAS ALSO HAD TO TAKE ANTIBIOTICS. SHE WANTS TO KNOW IF ANTIBIOTICS CAN REDUCE THE FFECTIVENESS OF BCG??

<drpeters> That is a good question, clearly some antibiotics can inhibit BCG in the test tube. However, we have no good data in human use that it effects the efficacy of BCG. In bladder cancer, we at times need to use antibiotics and do not hesitate to do this with BCG.

<icnmgrjill> QUESTION #16: BILL HAS A COMMENT ABOUT THE IMMUNE SYSTEM. HE SAYS THAT WHEN HE HAS COLD, HIS IC SYMPTOMS ARE GREATLY REDUCED. DOES THAT FIT WITH THE IMMUNE MODEL??

<drpeters> That is an interesting observation but we do not know the answer

<icnmgrjill> QUESTION #17: MARY HAS THE LAST QUESTION. SHE WANTS TO KNOW HOW LONG AFTER THE 6 WEEKS OF THERAPY COULD SOMEONE SEE IMPROVEMENT? IS IT 3 MONTHS FROM THE FIRST TREATMENT OR THE LAST TREATMENT?? OR IN BETWEEN?

<drpeters> In general the symptom improvement begins at the soonest 3 months from the last instillation. However, the majority of improvement occurs between the 3 and 6 month follow-up. When we followed patients over two years, the symptoms appear to continually improve in those who respond.

<icnmgrjill> SHE CONTINUES WITH HER QUESTION. ARE PATIENTS TREATED WITH ANYTHING ELSE DURING THAT 3-6 MONTH WAIT??

<drpeters> Patients can remain on their usual IC medications but cannot have any bladder instillations with other meds, i.e. DMSO. Clearly pain medication is OK.

<icnmgrjill> QUESTION #18: REBA HAD ONE LAST QUESTION. HOW DOES LIDOCAINE INTERFERE WITH BCG??

<drpeters> It has been shown in the lab that lidocaine jelly can kill bcg, thus we assume the same in humans

--------------- QUESTION & ANSWERS ENDS ----------------

<icnmgrjill> THANK YOU DR. PETERS! EXCELLENT PRESENTATION AND I MUST SAY THAT WE WERE ALL RIVETED. IT GIVES US ALL GREAT HOPE THAT WE HAVE TREATMENTS THAT APPEAR TO HOLDING UP WELL IN THE RESEARCH AND THAT OPTIONS WILL CLEARLY BE AVAILABLE IN THE FUTURE. LET ME TAKE OFF THE MODERATION SO THAT EVERYONE CAN SAY THANK YOU!

Special gratitude to Julie Halbur for coordinating this exceptional presentation.

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